This invention is a medical device principally for the treatment of insulin dependent diabetes (IDDM).
IDDM is an autoimmune disease of the pancreas, which results in the destruction of the Islets of Langerhans (IL). The IL contains two main types of endocrine cells: alpha cells which produce glucagon and beta cells which produce insulin. These antagonistic hormones increase and lower the blood sugar level (BSL) respectively, thereby keeping the BSL within the optimum range of 4 to 7 mmols per liter.
IDDM is generally treated by daily injections of insulin. As this involves the release of predetermined amounts of insulin into the bloodstream, however, the amount of carbohydrate (CHO) and exercise have to be carefully balanced against this to avoid the BSL going too low (hypoglycaemia) or too high (hyperglycaemia).
To maintain a reasonable balance many diabetics have to take several injections and blood tests a day. Even with close monitoring, however, hypoglycaemic episodes (‘hypos’) are virtually impossible to avoid altogether, and these are particularly dangerous during sleep, as they can quickly lead to unconsciousness or even coma.
If a diabetic's BSL is particularly erratic, an insulin pump may be used instead of traditional injections to provide a steadier release of insulin into the bloodstream. Some of the latest insulin pumps also employ a glucose sensor, which monitors the BSL to determine when and how much insulin should be released. The sensor works by detecting changes in the level of glucose in the interstitial fluid found between the body's cells (IFSL), and then feeding this information to a microprocessor.
One difficulty with existing insulin pumps is that they are situated outside the body, to allow the battery to be recharged and insulin and sensor parts to be replaced. As a result, there is a risk of infection at the insertion sites of the pump and the glucose sensor. There is also a risk that parts of the pump may become detached during sleep, and restless nights are not uncommon, particularly when there are problems with a diabetic's BSL. In addition, it may not be practical to keep the pump on all of the times during the day, for example when washing, swimming, during intimacy, or when taking part in certain sports.
The main problem with insulin pumps that employ glucose sensors is the inevitable delay between changes in the BSL and the IFSL. To compensate for this, the glucose sensor is controlled by a complicated computer programme, which requires data to be input regularly regarding BSL readings and the amount of exercise and CHO taken. Even with these safeguards, however, it is impossible to rule out hypos altogether, which may be acerbated if the pump continues to deliver insulin when the BSL is already dangerously low.
One final problem with pumps is something known as ketoacidosis, a potentially dangerous condition that can arise as a result of hyperglycaemia. It is known that the risk of ketoacidosis is higher with insulin pumps, as they cannot use longer-acting insulins, which provide some protection against this condition.
These problems with the conventional treatments of IDDM have led researchers to consider creating beta cells from a person's T cells and then implanting them in the patient's body. The new beta cells would then secrete insulin in response to changes in the BSL, removing the need for injections or insulin pumps altogether.
To date, techniques for growing large numbers of beta cells are still at a relatively early stage. In addition, as IDDM is an autoimmune disease, there is a high risk that the diabetic's immune system would destroy cells that were identical to the original beta cells. As a result, the implanted cells would have to be protected with a durable coating, which contained microscopic pores that were large enough to let insulin out but small enough to prevent the body's defence systems from entering. Although some protective coatings have been developed, these are also still some way from being perfected.
As with U.S. Pat. No. 4,538,616 of 3 Sep. 1985, this invention employs the principle of osmosis to drive the sensor mechanism. The former device failed, however, due to problems associated with placing a foreign body in the bloodstream, which were highlighted in International Patent WO 98/28605 of 2 Jul. 1998.
U.S. Pat. No. 4,538,616 also contemplated the use of a membrane that was impermeable to other solutes that affect the osmotic pressure of the blood, in particular sodium chloride and sodium lactate. As a result, the device could be adversely affected by changes in osmotic pressure caused by variations in these solutes.
Since U.S. Pat. No. 4,538,616, osmotic devices to control blood sugar level have been designed for use outside the blood stream. International Patent WO 98/28605 of 2 Jul. 1998, therefore, involved an osmotic transducer solely for use in the body tissues. It also does not overcome the problems created by other substances that can affect osmotic pressure, in particular sodium lactate. The device cannot therefore be used when lactic acid rises, e.g. during hard exercise (page 17, line 25).
International Patent WO 91/04704 A of 18 Apr. 1991 suggests an alternative mechanism for measuring osmolality, which would isolate changes in osmotic pressure that were caused by glucose alone. However, this sensing device is made of synthetic substances, and is therefore only suitable for use in the body tissues (‘interstitial regions’), as opposed to the bloodstream.
International Patent WO 03/061475 A is very similar to International Patent number WO 91/04704 A, but uses a more sophisticated arrangement of valve chambers to minimise the effects of bio-fouling (page 3, lines 11-13). Once again, therefore, it could not be used in the bloodstream for any length of time.